A 'Cure' for Peanut Allergy?

Attempting Oral Desensitization to Peanuts

Peanut allergy is a common and potentially life-threatening condition. To date, the primary means of preventing serious events has been peanut avoidance.

The PALISADE,^[1] a recent, large, double-blind, placebo-controlled, randomized trial, sought to determine whether a test agent containing 300 mg of peanut protein could produce desensitization in patients who were allergic to peanuts. The study was conducted at 66 international sites. The participants, aged 4 to 55 years, had peanut-specific immunoglobulin E levels above a predetermined threshold or a significant reaction on skin prick testing. Of interest, the final report focuses on the younger subjects (aged 4-17 years) because little efficacy was found among adults (aged ≤18 years) with peanut allergy.

During the baseline challenge, the subjects were given up to 100 mg of peanut protein (equal to one third of a peanut), and all had some degree of an allergic reaction. The randomization was 3:1, treatment:placebo. Both groups of subjects were given similar oral powders meant to be taken daily. Patients began on low doses, 0.5 mg/day, and escalated up to the amount they could tolerate, with a goal of 300 mg/day. Patients who were unable to reach the maintenance dose by week 40 were considered noncompleters. Those who reached the maintenance dose of 300 mg/day were expected to do so for at least 24 weeks. The primary endpoint was the ability to tolerate a single dose of at least 600 mg peanut protein, equal to approximately two peanuts.

PALISADE Study Findings

There were 496 participants, aged from 4 to 17 years, with a slight male majority of 57%. Most (72%) of the participants had experienced at least one previous anaphylaxis episode after peanut ingestion, and 53% had a history of asthma. This was a largely atopic group, with 66% having multiple food allergies.

There was a notable difference in the proportion of patients who could tolerate the final peanut protein challenge. In the treatment group, 67.2% were able to ingest the test dose of 600 mg peanut protein with no more than mild symptoms, but only 4% of the placebo group were able to do so.

Similarly, notable differences were found in the proportion of patients who were able to tolerate 300 mg (76.6% vs 8.1%) and the proportion who were able to tolerate 1000 mg (50.3% vs 2.4%) peanut powder at the end of the trial. Only 5% of the intervention group compared with 11% of the placebo group experienced a severe reaction during the exit food challenge. Rescue epinephrine during the final food challenge was required by 10% of the intervention group compared with 53% of the placebo group. There was a differential in withdrawal from the trial, however, with 11.6% of the active treatment group compared with 2.4% of placebo group discontinuing the trial because of adverse events. In addition, 14% of the intervention group and 6.5% of the placebo group required rescue epinephrine during the year-long treatment phase. The authors concluded that the study preparation induced desensitization among the children who completed the trial.

Viewpoint

I have said it before, but it is worth repeating: Much, although certainly not all, of what we thought we knew for the past 20 years about how to prevent food allergies, particularly nut allergies, is exactly wrong. And this stands out as an example of when the prevailing wisdom has reversed completely.

In an accompanying editorial, Perkin^[2] succinctly identifies several take-home points. First, the notable percentage of subjects who required rescue epinephrine doses in both groups, but especially the treatment group, demonstrates that this process should be carefully monitored. For now, that means that this is not the purview of primary care physicians. Second, daily dosing for 12 months is difficult to maintain, and the study does not establish how long protection might last should a patient discontinue therapy. Third, long-term ingestion with even low-doses of a substance by someone who is sensitive to it could induce other allergic disease, including mucosal eosinophilia, down the line.

Regardless, for patients who fear eating outside of the home, where they have less control over avoidance of an allergen, this therapy could certainly be life-saving. And I suspect there is no shortage of patients willing to participate in such trials for the prospect of gaining protection from inadvertent peanut exposure.

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